Premium
Factor XII activation is essential to sustain the procoagulant effects of particulate matter
Author(s) -
KILINÇ E.,
VAN OERLE R.,
BORISSOFF J. I.,
OSCHATZ C.,
GERLOFSNIJLAND M. E.,
JANSSEN N. A.,
CASSEE F. R.,
SANDSTRÖM T.,
RENNÉ T.,
TEN CATE H.,
SPRONK H. M. H.
Publication year - 2011
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2011.04280.x
Subject(s) - thrombin , chemistry , coagulation , factor xii , proteases , thrombin generation , tissue factor , platelet , medicine , biochemistry , enzyme
See also Mutch NJ. Emerging roles for factor XII in vivo . This issue, pp 1355–8. Summary. Background: Particulate matter (PM) is a key component of ambient air pollution and has been associated with an increased risk of thrombotic events and mortality. The underlying mechanisms remain unclear. Objectives: To study the mechanisms of PM‐driven procoagulant activity in human plasma and to investigate mainly, the coagulation driven by ultrafine particles (UFPs; < 0.1 μm) in genetically modified mice. Methods: Thrombin generation in response to PM of different sizes was assessed in normal human platelet‐poor plasma, as well as in plasmas deficient in the intrinsic pathway proteases factors XII (FXII) or XI (FXI). In addition, UFPs were intratracheally instilled in wild‐type (WT) and FXII‐deficient (FXII −/− ) mice and plasma thrombin generation was analyzed in plasma from treated mice at 4 and 20 h post‐exposure. Results: In normal human plasma, thrombin generation was enhanced in the presence of PM, whereas PM‐driven thrombin formation was completely abolished in FXII‐ and FXI‐deficient plasma. UFPs induced a transient increase in tissue factor (TF)‐driven thrombin formation at 4 h post‐instillation in WT mice compared with saline instillation. Intratracheal instillation of UFPs resulted in a procoagulant response in WT mice plasma at 20 h, whereas it was entirely suppressed in FXII −/− mice. Conclusions: Overall, the data suggest that PM promotes its early procoagulant actions mostly through the TF‐driven extrinsic pathway of coagulation, whereas PM‐driven long lasting thrombogenic effects are predominantly mediated via formation of activated FXII. Hence, FXII‐driven thrombin formation may be relevant to an enhanced thrombotic susceptibility upon chronic exposure to PM in humans.